52 F.3d 1043 (Fed. Cir. 1995), 94-1026, Glaxo Inc. v. Novopharm Ltd.

Docket Nº:94-1026.
Citation:52 F.3d 1043
Party Name:34 U.S.P.Q.2d 1565 GLAXO INC. and Glaxo Group Limited, Plaintiffs-Appellees, v. NOVOPHARM LTD., Defendant-Appellant.
Case Date:April 21, 1995
Court:United States Courts of Appeals, Court of Appeals for the Federal Circuit

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52 F.3d 1043 (Fed. Cir. 1995)

34 U.S.P.Q.2d 1565

GLAXO INC. and Glaxo Group Limited, Plaintiffs-Appellees,


NOVOPHARM LTD., Defendant-Appellant.

No. 94-1026.

United States Court of Appeals, Federal Circuit

April 21, 1995

Rehearing Denied; Suggestion for Rehearing In Banc Declined

June 21, 1995.[*]

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[Copyrighted Material Omitted]

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Stephen B. Judlowe, Hopgood, Calimafde, Kalil, Blaustein & Judlowe, New York City, argued for plaintiffs-appellees. With him on the brief were William G. Todd and Janet B. Linn. Also on the brief were Steven P. Lockman, Arnold & Porter, Washington, DC, and Joseph W. Eason, Moore & Van Allen, Raleigh, NC, of counsel.

Robert F. Green, Leydig, Voit & Mayer, LTD., Chicago, IL, argued for defendant-appellant. With him on the brief were John E. Rosenquist and Jeffrey S. Ward.

Before ARCHER, Chief Judge, RICH, and MAYER, Circuit Judges.

Opinion for the court filed by Circuit Judge RICH. Dissenting opinion filed by Circuit Judge MAYER.

RICH, Circuit Judge.

Novopharm Ltd. (Novopharm) appeals the judgment of the United States District Court for the Eastern District of North Carolina, Glaxo, Inc. v. Novopharm Ltd., 830 F.Supp. 871, 29 USPQ2d 1126 (E.D.N.C.1993), that United States Patent No. 4,521,431 was not invalid and was infringed, and enjoining Novopharm from the commercial manufacture or sale of the patented crystalline form of ranitidine hydrochloride. We affirm.


Glaxo Inc. and Glaxo Group Ltd. (collectively Glaxo) are the owner and exclusive United States licensee, respectively, of United States Patent No. 4,521,431 ('431 patent). The '431 patent claims a specific crystalline form of the compound ranitidine hydrochloride, designated as "Form 2," which Glaxo markets as an antiulcer medication under the brand name Zantac. 1 The '431 patent issued on June 4, 1985.

In 1976, Glaxo chemists investigating potential antiulcer medications synthesized an aminoalkyl furan derivative, later named ranitidine,

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which proved to be a potent histamine blocker, inhibiting the secretion of stomach acid. Later that year, Glaxo filed an application for a patent on ranitidine in the United Kingdom. It followed with an application for a United States patent, which issued as No. 4,128,658 ('658 patent) on December 5, 1978. The '658 patent claims a number of structurally similar compounds, including ranitidine and its hydrochloride salt. It discloses one method for preparing ranitidine hydrochloride, set forth in the '658 patent as Example 32. 2

Glaxo prepared large quantities of ranitidine hydrochloride between 1977 and 1980 for use in toxicology and clinical studies. Instead of using the process of Example 32, however, Glaxo's chemists prepared this material using a similar process that they labelled Process 3A. They later developed a more efficient method that they called Process 3B. Until April 15, 1980, both Process 3A and Process 3B yielded ranitidine hydrochloride identical in all respects to that originally produced using the Example 32 procedure.

On that date, however, Glaxo's Derek Crookes used Process 3B to prepare crystalline ranitidine hydrochloride that was visibly different from all previous batches of the salt. The difference was confirmed by infra-red (IR) spectroscopy and x-ray powder diffraction, which revealed that the new product was a crystalline form, or polymorph, of ranitidine hydrochloride that differed from the previously known form. Glaxo began to refer to this new polymorph as Form 2 ranitidine hydrochloride (designating the old polymorph as Form 1).

Because Form 2 had better filtration and drying properties, making it better suited for commercial applications, Glaxo decided to proceed with commercialization of Form 2 rather than Form 1. Form 2 was hampered by poor flow properties, however, which made the material difficult to measure and dispense in its pure form. Accordingly, Glaxo scientists developed a novel azeotroping process 3 to granulate the Form 2 salt, which made it much easier to make into pharmaceutical compositions. This process was the subject of a British patent application that Glaxo eventually abandoned without disclosing the process to the public.

Glaxo filed a patent application covering Form 2 ranitidine hydrochloride in the United Kingdom on October 1, 1980. It filed a United States application thereon the next year, which eventually issued as the '431 patent in suit. When George Graham Brereton, Glaxo's patent officer initially charged with pursuing the United States application, learned of the azeotropic granulation process and Glaxo's desire to keep that process secret, he recommended that Glaxo not claim pharmaceutical compositions of the Form 2 salt for fear of violating the best mode requirement. Brereton apparently believed that disclosure of the azeotroping process would be necessary because it was the best way to make the Form 2 salt for use in preparing pharmaceutical compositions. He later moved to another position at Glaxo. The U.S. application was eventually amended to include pharmaceutical composition claims, but Glaxo did not amend the specification to disclose the azeotroping process.

On August 9, 1991, Novopharm Ltd. filed an Abbreviated New Drug Application (ANDA) with the Food and Drug Administration

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(FDA), seeking FDA approval to manufacture and sell a generic version of Form 2 ranitidine hydrochloride beginning December 5, 1995, the expiration date of the '658 patent, well before the expiration date of the '431 patent in 2002. Glaxo filed this suit for patent infringement on November 13, 1991, alleging technical infringement of claims 1 and 2 of the '431 patent by the ANDA filing as provided in 35 U.S.C. Sec. 271(e)(2) (1988). Novopharm admitted infringement of the claims, but contended that the '431 patent was invalid because it was anticipated by the disclosure of the '658 patent.

Novopharm later amended its answer to add the defense of inequitable conduct arising from alleged false and misleading affidavits provided to the U.S. Patent and Trademark Office (PTO) during prosecution of the applications from which the '431 patent issued. Finally, on June 21, 1993, Novopharm sought summary judgment based on a third defense, Glaxo's alleged failure to disclose the best mode of practicing the claimed invention. The trial court denied the motion, and the case was tried to the court beginning on August 9, 1993.

On the question of anticipation, the court found that Novopharm had not carried its burden of proving by clear and convincing evidence that practice of Example 32 of the '658 patent always produced Form 2 ranitidine hydrochloride, so that Form 2 was not inherently disclosed by Example 32. As for inequitable conduct, the court agreed with Novopharm that the affidavits presented to the examiner were misleading and material, but it found that Novopharm had failed to prove any deceptive intent. The court also concluded that there was no violation of the best mode requirement because Novopharm had not proved that Crookes, the inventor, knew of the best mode, the statute and this court's precedent providing that knowledge by the inventor himself is required. Accordingly, the court held that the '431 patent was not invalid, was enforceable and infringed, and ordered that Novopharm refrain from commercial manufacture or sale of Form 2 ranitidine hydrochloride before the '431 patent expires. Novopharm appeals.


I. Example 32, Anticipation

We consider first Novopharm's argument that the district court erred in holding that Novopharm did not prove that the claims in suit of the '431 patent were anticipated by Example 32 of the '658 patent. Anticipation is a factual matter, which we review under the clearly erroneous standard. Diversitech Corp. v. Century Steps Inc., 850 F.2d 675, 677, 7 USPQ2d 1315, 1317 (Fed.Cir.1988). A claim is anticipated and therefore invalid only when a single prior art reference discloses each and every limitation of the claim. 35 U.S.C. Sec. 102(a) (1988); Kloster Speedsteel AB v. Crucible Inc., 793 F.2d 1565, 1571, 230 USPQ 81, 84 (Fed.Cir.1986). The disclosure need not be express, but may anticipate by inherency where it would be appreciated by one of ordinary skill in the art. Continental Can Co. USA Inc. v. Monsanto Co., 948 F.2d 1264, 1268, 20 USPQ2d 1746, 1749 (Fed.Cir.1991).

Novopharm maintains that the invention claimed in the '431 patent, ranitidine hydrochloride in its Form 2 crystalline polymorph, is inherently disclosed in the '658 patent because the practice of Example 32 always yields ranitidine hydrochloride in its Form 2 polymorph. Novopharm's experts performed the process disclosed in Example 32 of the '658 patent thirteen times and each time they made Form 2 crystals, not Form 1 as Glaxo claims.

But the district court found that the practice of Example 32 could yield crystals of either polymorph. It specifically found that Glaxo's David Collin originally made Form 1 by practicing Example 32, and that Glaxo's expert, Nicholas Crouch, did too. 4 We are not persuaded that these findings are clearly

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erroneous. The district court correctly rejected the anticipation defense.

II. Inequitable Conduct

Novopharm contends that the trial court erred as a matter of law in declining to infer an intent to deceive from Glaxo's material misrepresentations to the PTO. The charge of inequitable conduct arises from a declaration submitted by John Harold Hunt, the head of Glaxo's spectroscopy group, in response to a rejection in light of the product of Example 32 of the '658 patent. 5

To prevail on its inequitable conduct defense, Novopharm had to show by clear and convincing evidence that Glaxo...

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